College of Forensic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, PR China; The Key Laboratory of Health Ministry for Forensic Science, Xi'an Jiaotong University, Shaanxi, PR China.
Shaanxi Police College, Xi'an, Shaanxi, 710021, PR China.
Neurosci Lett. 2019 Aug 10;707:134303. doi: 10.1016/j.neulet.2019.134303. Epub 2019 May 30.
MicroRNAs (miRNAs) are gene expression regulators that play an important role in drug addiction. We previously reported miR-204-3p was the only up-regulated miRNA in the nucleus accumbens (NAc) in methamphetamine (METH)-sensitized mice. In this study, we are reporting a miR-204-3p potential mechanism in METH sensitization. We first measured the expression changes of miR-204-3p in the NAc of METH- sensitized mice. Then we predicted the targets of miR-204-3p by bioinformatics tools and combined the potential targets with the METH-responsive genes from the ArrayExpress database. KEGG pathway analyses were performed to investigate the prospective mechanisms and four enriched genes were validated by RT-PCR. As a result, miR-204-3p showed a shift from down-regulation to up-regulation in the NAc from the development to the expression of METH sensitization. Bioinformatics analysis predicted 1834 putative targets, 259 of which were differentially expressed in the NAc in response to METH. These targets were significantly enriched in axon guidance (P = 9.59 × 10). Four putative targets (Sema3A, Plxna4, Rac1, and Pak3) enriched in axon guidance also exhibited significant changes in the NAc after METH challenge injection. Moreover, expression levels of miR-204-3p, Sema3A and Plxna4 exhibited a negative association in the expression of METH sensitization. It appeared that miR-204-3p may be involved in the expression of METH sensitization by regulating the expression of Sema3A and Plxna4. Our study provided a potential network of miR-204-3p-axon guidance in the NAc in the expression of METH-induced behavioral sensitization.
微小 RNA（miRNAs）是基因表达调控因子，在药物成瘾中发挥重要作用。我们之前报道过，在甲基苯丙胺（METH）敏化小鼠的伏隔核（NAc）中，miR-204-3p 是唯一上调的 miRNA。在这项研究中，我们报告了 miR-204-3p 在 METH 敏化中的潜在机制。我们首先测量了 METH 敏化小鼠 NAc 中 miR-204-3p 的表达变化。然后，我们通过生物信息学工具预测了 miR-204-3p 的靶标，并将潜在靶标与 ArrayExpress 数据库中的 METH 反应基因结合。KEGG 通路分析用于研究潜在的机制，四个富集的基因通过 RT-PCR 进行验证。结果显示，miR-204-3p 在从 METH 敏化的发展到表达的过程中，在 NAc 中的表达从下调转变为上调。生物信息学分析预测了 1834 个可能的靶标，其中 259 个在 METH 反应的 NAc 中差异表达。这些靶标在轴突导向中显著富集（P = 9.59×10）。在轴突导向中富集的四个可能的靶标（Sema3A、Plxna4、Rac1 和 Pak3）在 METH 挑战注射后在 NAc 中也表现出显著变化。此外，miR-204-3p、Sema3A 和 Plxna4 的表达水平在 METH 敏化的表达中呈负相关。似乎 miR-204-3p 通过调节 Sema3A 和 Plxna4 的表达参与了 METH 敏化的表达。我们的研究提供了一个潜在的 miR-204-3p-轴突导向网络，该网络在 METH 诱导的行为敏化的 NAc 表达中起作用。
